Graft Loss in Pediatric and Young Adult Kidney Transplantation in New Zealand: Who Is at Greatest Risk and When?

BACKGROUND: Much is reported regarding the detrimental effect of transfer to adult services for adolescent and young adult (AYA) kidney transplant (KT) recipients. However, AYA recipient age independent of time post-KT, and not relating to transfer of care, is also a strong predictor of graft loss. We assessed KT graft survival if experiencing solely pediatric (PO) or adult services (AO) versus transfer from pediatric to adult services (PTA). METHODS: A retrospective cohort analysis of all first kidney transplant recipients between birth-24 years of age, from 2000 to 2019 in New Zealand. Participant identification and data were obtained via the Australia and New Zealand Dialysis and Transplantation registry. Primary outcome was graft survival stratified by service type. Cox proportional hazard modeling assessed independent risk factors of graft loss. RESULTS: Two hundred forty-four children and AYA with a median follow-up of 7.3 years were included. Graft survival stratified by service provision group was not different. The incidence rate of graft loss was 37, 34, and 45 per 1000 persons per year for PO, PTA, and AO respectively. Crude age-specific graft failure rates were highest for 22-24-year-olds with inferior outcomes starting from age 16, peaking at 24 years. CONCLUSIONS: Older adolescence and young adulthood reflect a high-risk period for KT loss. Transfer to adult services was not associated with worse graft survival compared to those experiencing either AO or PO alone. Improved models of care are needed to improve graft survival in this vulnerable population within New Zealand.

Phase I study of capecitabine combined with radioembolization using yttrium-90 resin microspheres (SIR-Spheres) in patients with advanced cancer.

BACKGROUND: This was a prospective single-centre, phase I study to document the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), and the recommended phase II dose for future study of capecitabine in combination with radioembolization. METHODS: Patients with advanced unresectable liver-dominant cancer were enrolled in a 3+3 design with escalating doses of capecitabine (375-1000 mg/m(2) b.i.d.) for 14 days every 21 days. Radioembolization with (90)Y-resin microspheres was administered using a sequential lobar approach with two cycles of capecitabine. RESULTS: Twenty-four patients (17 colorectal) were enrolled. The MTD was not reached. Haematologic events were generally mild. Common grade 1/2 non-haematologic toxicities included transient transaminitis/alkaline phosphatase elevation (9 (37.5%) patients), nausea (9 (37.5%)), abdominal pain (7 (29.0%)), fatigue (7 (29.0%)), and hand-foot syndrome or rash/desquamation (7 (29.0%)). One patient experienced a partial gastric antral perforation with a capecitabine dose of 750 mg/m(2). The best response was partial response in four (16.7%) patients, stable disease in 17 (70.8%) and progression in three (12.5%). Median time to progression and overall survival of the metastatic colorectal cancer cohort was 6.4 and 8.1 months, respectively. CONCLUSIONS: This combined modality treatment was generally well tolerated with encouraging clinical activity. Capecitabine 1000 mg/m(2) b.i.d. is recommended for phase II study with sequential lobar radioembolization.

Living with COPD and its psychological effects on participating in community-based physical activity in Brazil: a qualitative study. Findings from the Breathe Well group.

Physical activity (PA) improves dyspnoea, psychological wellbeing and quality of life (QoL) for people with COPD reducing their risk of exacerbation. However, engagement in PA is low especially amongst those with anxiety and depression, and PA programmes are limited in countries with limited resources such as Brazil. We explored perceptions of 21 people with COPD about the impact of their disease on taking part in community-based PA programmes in Sao Paulo, Brazil through semi-structured telephone interviews from October 2020 to April 2021. Discussions were audio-recorded, transcribed, and analysed using the Framework method. Five themes were identified: Knowledge about COPD and its management; Self-perception of life with COPD; Knowledge and experiences of depression and anxiety; Opinions on PA and repercussions of COVID-19. PA was considered to be important in bringing physical and mental health benefits but there were barriers in accessibility of formal PR programmes and therefore local community PA programmes were considered to be important. People with mental health conditions tended to view PA more negatively. COVID-19 had reduced PA opportunities, access to COPD treatment and social interaction, and was associated with more exacerbations and emotional suffering. In general, this study showed an urgent need to improve knowledge about COPD and its risk factors and management among both patients, the public and primary healthcare professionals. We provide important content for the formulation of public policies for the implementation of specific activity programmes for people with COPD in community spaces using local resources and intersectoral partnerships.

Dimethyl fumarate decreases short-term but not long-term inflammation in a focal EAE model of neuroinflammation.

BACKGROUND: Dimethyl fumarate (DMF) is an oral immunomodulatory drug used in the treatment of autoimmune diseases. Here, we sought to study whether the effect of DMF can be detected using positron emission tomography (PET) targeting the 18-kDa translocator protein (TSPO) in the focal delayed-type hypersensitivity rat model of multiple sclerosis (fDTH-EAE). The rats were treated orally twice daily from lesion activation (day 0) with either vehicle (tap water with 0.08% Methocel, 200 µL; control group n = 4 (3 after week four)) or 15 mg/kg DMF (n = 4) in 0.08% aqueous Methocel (200 µL) for 8 weeks. The animals were imaged by PET using the TSPO tracer [18F]GE-180 in weeks 0, 1, 2, 4, 8, and 18 following lesion activation, and the non-displaceable binding potential (BPND) was calculated. Immunohistochemical staining for Iba1, CD4, and CD8 was performed in week 18, and in separate cohorts of animals, following 2 or 4 weeks of treatment. RESULTS: Using the fDTH-EAE model, DMF reduced the [18F]GE-180 BPND in the DMF-treated animals compared to control animals after 1 week of treatment (two-tailed unpaired t test, p = 0.031), but not in weeks 2, 4, 8, or 18 when imaged in vivo by PET. Immunostaining for Iba1 showed that DMF had no effect on the perilesional volume or the core lesion volume after 2 or 4 weeks of treatment, or at 18 weeks. However, the optical density (OD) measurements of CD4+ staining showed reduced OD in the lesions of the treated rats. CONCLUSIONS: DMF reduced the microglial activation in the fDTH-EAE model after 1 week of treatment, as detected by PET imaging of the TSPO ligand [18F]GE-180. However, over an extended time course, reduced microglial activation was not observed using [18F]GE-180 or by immunohistochemistry for Iba1+ microglia/macrophages. Additionally, DMF did affect the infiltration of CD4+ and CD8+ T-lymphocytes at the fDTH-EAE lesion.

Enhancement of antibacterial activity through phyto-fabrication of silver nanoparticles with Ficus thonningii aqueous extracts.

The World Health Organisation reports higher levels of bacterial resistance to cephalosporins and carbapenems of above 54%. The sufficient redox capabilities of Ficus thonningii phytochemicals for Ag+  reduction to Ag0 and ultimately aggregation to nucleation are exploited for the first time in attempting to enhance the antibacterial activity. Solution colour change to brown due to surface plasmon resonance phenomenon confirmed nanoparticle fabrication with a UV/Vis absorption peak at 426 nm. Fourier Transform Infrared spectra revealed functional groups (C=C at 1620-1680 cm-1 ; C=H at 1400-1600 cm-1 aromatics) for encapsulation, stabilisation, and reduction of the silver ion. The Dynamic Light Scattering technique verified F. thonningii encapsulated silver nanoparticles particle size of 57.84 nm with a negative zeta potential (-19.8 mV) as proof of stability. The surface, shape and topographical features were shown by Scanning Electron Microscopy as spherical orientations. An enhanced antimicrobial efficacy was displayed by the nanoparticles (inhibition zones of 26.1, 24.1 and 15.2 mm from 11.5, 10.6 and 6.5 mm) for Staphylococcus aureus, Streptococcus pyrogenes and Escherichia coli, respectively, compared to Flucloxacillin standard that was in the ranges of 21.5, 23.5 and 25.7 mm. The enhanced potency provides a basis for diversified approaches of generating novel drugs for treating bacterial infections.

Accuracy and economic evaluation of screening tests for undiagnosed COPD among hypertensive individuals in Brazil.

In Brazil, prevalence of diagnosed COPD among adults aged 40 years and over is 16% although over 70% of cases remain undiagnosed. Hypertension is common and well-recorded in primary care, and frequently co-exists with COPD because of common causes such as tobacco smoking, therefore we conducted a cross-sectional screening test accuracy study in nine Basic Health Units in Brazil, among hypertensive patients aged ≥40 years to identify the optimum screening test/combinations to detect undiagnosed COPD. We compared six index tests (four screening questionnaires, microspirometer and peak flow) against the reference test defined as those below the lower limit of normal (LLN-GLI) on quality diagnostic spirometry, with confirmed COPD at clinical review. Of 1162 participants, 6.8% (n = 79) had clinically confirmed COPD. Peak flow had a higher specificity but lower sensitivity than microspirometry (sensitivity 44.3% [95% CI 33.1, 55.9], specificity 95.5% [95% CI 94.1, 96.6]). SBQ performed well compared to the other questionnaires (sensitivity 75.9% [95% CI 65.0, 84.9], specificity 59.2% [95% CI 56.2, 62.1]). A strategy requiring both SBQ and peak flow to be positive yielded sensitivity of 39.2% (95% CI 28.4, 50.9) and specificity of 97.0% (95% CI 95.7, 97.9). The use of simple screening tests was feasible within the Brazilian primary care setting. The combination of SBQ and peak flow appeared most efficient, when considering performance of the test, cost and ease of use (costing £1690 (5554 R$) with 26.7 cases detected per 1,000 patients). However, the choice of screening tests depends on the clinical setting and availability of resources.ISRCTN registration number: 11377960.

Accuracy of Vitalograph lung monitor as a screening test for COPD in primary care.

Microspirometry may be useful as the second stage of a screening pathway among patients reporting respiratory symptoms. We assessed sensitivity and specificity of the Vitalograph® lung monitor compared with post-bronchodilator confirmatory spirometry (ndd Easy on-PC) among primary care chronic obstructive pulmonary disease (COPD) patients within the Birmingham COPD cohort. We report a case-control analysis within 71 general practices in the UK. Eligible patients were aged ≥40 years who were either on a clinical COPD register or reported chronic respiratory symptoms on a questionnaire. Participants performed pre- and post-bronchodilator microspirometry, prior to confirmatory spirometry. Out of the 544 participants, COPD was confirmed in 337 according to post-bronchodilator confirmatory spirometry. Pre-bronchodilator, using the LLN as a cut-point, the lung monitor had a sensitivity of 50.5% (95% CI 45.0%, 55.9%) and a specificity of 99.0% (95% CI 96.6%, 99.9%) in our sample. Using a fixed ratio of FEV1/FEV6 < 0.7 to define obstruction in the lung monitor, sensitivity increased (58.8%; 95% CI 53.0, 63.8) while specificity was virtually identical (98.6%; 95% CI 95.8, 99.7). Within our sample, the optimal cut-point for the lung monitor was FEV1/FEV6 < 0.78, with sensitivity of 82.8% (95% CI 78.3%, 86.7%) and specificity of 85.0% (95% CI 79.4%, 89.6%). Test performance of the lung monitor was unaffected by bronchodilation. The lung monitor could be used in primary care without a bronchodilator using a simple ratio of FEV1/FEV6 as part of a screening pathway for COPD among patients reporting respiratory symptoms.

Cessation of anti-VLA-4 therapy in a focal rat model of multiple sclerosis causes an increase in neuroinflammation.

BACKGROUND: Positron emission tomography (PET) can be used for in vivo evaluation of the pathology associated with multiple sclerosis. We investigated the use of longitudinal PET imaging and the 18-kDa translocator protein (TSPO) binding radioligand [18F]GE-180 to detect changes in a chronic multiple sclerosis-like focal delayed-type hypersensitivity experimental autoimmune encephalomyelitis (fDTH-EAE) rat model during and after anti-VLA-4 monoclonal antibody (mAb) treatment. Thirty days after lesion activation, fDTH-EAE rats were treated with the anti-VLA-4 mAb (n = 4) or a control mAb (n = 4; 5 mg/kg, every third day, subcutaneously) for 31 days. Animals were imaged with [18F]GE-180 on days 30, 44, 65, 86 and 142. Another group of animals (n = 4) was used for visualisation the microglia with Iba-1 at day 44 after a 2-week treatment period. RESULTS: After a 2-week treatment period on day 44, there was a declining trend (p = 0.067) in [18F]GE-180-binding in the anti-VLA-4 mAb-treated animals versus controls. However, cessation of treatment for 4 days after a 31-day treatment period increased [18F]GE-180 binding in animals treated with anti-VLA-4 mAb compared to the control group (p = 0.0003). There was no difference between the groups in TSPO binding by day 142. CONCLUSIONS: These results demonstrated that cessation of anti-VLA-4 mAb treatment for 4 days caused a transient rebound increase in neuroinflammation. This highlights the usefulness of serial TSPO imaging in the fDTH-EAE model to better understand the rebound phenomenon.

Detection of C-polysaccharide in serum of patients with Streptococcus pneumoniae bacteraemia.

AIM: To investigate the fate of Streptococcus pneumoniae C-polysaccharide antigen in serum in patients with S pneumoniae bacteraemia. METHOD: In vitro dissociation experiments were performed to demonstrate that C-polysaccharide was masked by ligands in normal and acute phase serum. Serum samples from 22 patients with S pneumoniae bacteraemia were treated to dissociate immune complexes and then tested for C-polysaccharide by enzyme linked immunosorbent assay (ELISA). RESULTS: C-polysaccharide antigen was masked in normal and acute phase serum but could be released by EDTA treatment and detected by ELISA. Antigen was found in six patients ranging in concentration from 2.5 to 200 ng/ml. Patients with detectable antigen were more likely to die than those in whom antigen was not detected. CONCLUSION: This study demonstrates that C-polysaccharide antigen commonly circulates in patients with S pneumoniae bacteraemia but its presence is masked by ligands present in serum.

An outbreak of penicillin resistant Streptococcus pneumoniae investigated by a polymerase chain reaction based genotyping method.

AIMS: To characterise the genotypes of penicillin resistant Streptococcus pneumoniae infecting patients in a care of the elderly ward and to study its transmission in a hospital environment. METHODS: Isolates of S pneumoniae were cultured from specimens obtained from patients who had been admitted to a care of the elderly ward where an outbreak had occurred. Penicillin resistant S pneumoniae were also obtained from a series of surveillance throat swabs taken from patients in the same ward. In addition, all penicillin resistant S pneumoniae isolated from specimens submitted for culture at the time of the outbreak were included. Four sensitive strains isolated from a routine microbiology laboratory were included as controls. A simple polymerase chain reaction (PCR) based genotyping method for the penicillin binding protein (PBP) genes 1a, 2x, and 2b was used to characterise the genotypes. RESULTS: Nine patients were infected with serotype 9 S pneumoniae. Four of these patients died; two deaths were directly attributable to the infection. Tested against a battery of haemolytic streptococci and other organisms found in the respiratory tract, only two false positive reactions for PBP 2x were found among S mitis. The method demonstrated that the outbreak strain had altered PBP 1a, 2b, and 2x genes, a pattern clearly distinguishable from other penicillin resistant strains isolated at the same time. CONCLUSIONS: This method is simple to perform and would enable many laboratories to characterise the genotype of penicillin resistant S pneumoniae and investigate transmission in their hospitals.

Diagnosis of Streptococcus pneumoniae pneumonia by quantitative enzyme linked immunosorbent assay of C-polysaccharide antigen.

AIMS: To evaluate the use of a quantitative enzyme linked immunosorbent assay (ELISA) detecting C-polysaccharide (PnC) antigen in sputum for the diagnosis of Streptococcus pneumoniae infection. METHODS: Specimens of sputum from 60 patients with acute community and hospital acquired pneumonia and infective exacerbations of obstructive airways disease were examined by semiquantitative culture and antigen ELISA. RESULTS: Using a cutoff value of 1 microgram/ml PnC antigen for a positive result, the sensitivity of this assay was 90.3%, specificity 93.1%, predictive value of a positive result was 93.5%, and the predictive value of a negative result 89.6%. CONCLUSIONS: Quantitation of C-polysaccharide antigen in sputum by ELISA distinguishes between carriage of oral bacteria which express PnC-like antigen and infection with S pneumoniae and compares favourably with other diagnostic methods.

Phosphorylcholine-containing antigens in bacteria from the mouth and respiratory tract.

Phosphorylcholine (PC)-containing antigens were sought in 269 bacterial isolates from the mouth and respiratory tract by an enzyme immunoassay method. Only 41 (15%) isolates were PC-positive and of these 29 (70%) were strains of Haemophilus influenzae. Other species that produced positive results included two of five isolates of Gemella haemolysans, two of five isolates of Micrococcus spp., and a single strain each of Bacillus sp., Corynebacterium jeikeium, Lactococcus sp. and H. parainfluenzae. The presence of PC-containing antigens in H. influenzae may be an important source of cross-reaction in antigen detection techniques that detect the C-polysaccharide antigen of Streptococcus pneumoniae in respiratory specimens and would result in false positive results.

A comparison of four culture methods for diagnosing infection in continuous ambulatory peritoneal dialysis.

Dialysate effluent from 41 patients presenting with 54 episodes of CAPD peritonitis was examined by four culture techniques, three employing methods for the lysis of peritoneal leucocytes. The most efficient method employed a distilled water lysis-centrifugation technique (81% of episodes culture-positive). Filtration (without leucocyte lysis) was less effective (74% culture-positive). The results of a mechanical leucocyte lysis technique were less satisfactory still, the culture positive rate of 74% being compromised by the recovery of the infecting organism in low numbers, and by an association with a high incidence of plate contamination. The results of a bile-salt lysis technique were the least satisfactory (67% culture-positive).

A critical analysis of the rabbit eye irritation test variability and its impact on the validation of alternative methods.

Determining the validity of alternative methods as replacements for the rabbit eye irritation tests is a goal of the scientific, regulatory and political communities and is being evaluated in several studies. The results from the Draize rabbit eye test are used as a standard against which to compare the performance of the in vitro methods. However, the quantitative performance of the modern Draize eye test is unknown. This paper is a review of the findings of a previous study to estimate the historical variability and a comparison with more contemporary data in order to estimate the performance of the modern methods. The question of whether it is practical to obtain an accurate description of in vivo variability of the modern Draize test is considered by calculating the size of the interlaboratory study that would be required to determine whether variability had changed since 1971. The impact that in vivo variability has on the validation of alternative methods is then discussed. The authors conclude that validation studies have a greater chance of success if the alternative methods are soundly based on mechanisms of toxicity operating in vivo, the Draize data are well defined with regard to their variability, the goals of the study are realistic and the customers of the study are in broad agreement with the study design and the in vivo data used as the reference test set.

Threshold for classification as a skin sensitizer in the local lymph node assay: a statistical evaluation.

For more than 15 years, the murine local lymph node assay (LLNA) has undergone development, evaluation and validation as an alternative approach to the predictive identification of skin sensitizing chemicals. The criteria by which sensitizing chemicals are distinguished from those without significant skin sensitising hazard were developed empirically and were based on experience rather than a mathematical formula or statistical method. The current practice is to classify, as skin sensitizers, those chemicals which at one or more test concentrations stimulate a threefold or greater increase in the proliferative activity in draining lymph node cells. Despite the apparent confirmation of the utility of this approach from the extensive data available, there has not previously been any attempt to substantiate the accuracy of this criterion. In this present investigations, data from 134 chemicals tested in the LLNA and in the guinea pig and/or for which there exists clear evidence relating to human skin sensitization potential, have been subjected to a rigorous statistical evaluation using Receiver Operating Characteristic (ROC) curves. Whether the analysis is based on a comparison with guinea pig or human data, the results indicate that the empirically derived threefold threshold is an acceptable practical value for hazard identification.

A new isoenzyme of lactate dehydrogenase associated with sickle cell hemoglobin.

Electrophoretic fractionation of lactate dehydrogenase in the cytoplasm of red blood cells containing various types of hemoglobin has revealed a sixth isoenzyme occurring regularly in individuals in whom the major part of the hemoglobin is of the sickle cell type. The newly discovered fraction occurs between the normally present third and fourth components. This discovery marks the first time that an additional lactate dehydrogenase isoenzyme has been found in connection with a clinical abnormality. The isoenzyme may serve as a genetic and clinical marker.

Chordoma: diagnosis by fine-needle aspiration biopsy with histologic, immunocytochemical, and ultrastructural confirmation.

Five cases of chordoma, diagnosed by fine-needle aspiration (FNA) biopsy, are presented. Four cases were histologically confirmed, and in one, immunocytochemical and ultrastructural studies were performed on both the aspirate and tissue specimen. Four cases presented as sacral masses, while in the fifth case, a destructive lesion of the clivus extended into the soft tissues of the lateral neck. A spectrum of cytomorphologic features was encountered including the presence of abundant microtissue fragments and cells in a dissociate pattern, often with abundant metachromatic extracellular matrix. Stellate and cuboidal cells often contained intracytoplasmic vacuoles of varying sizes. Intranuclear inclusions, mitotic figures, and anisonucleosis were prominent features of several cases. Immunoperoxidase studies on a single case demonstrated cytoplasmic staining for low- and high-molecular-weight cytokeratins, vimentin, and epithelial membrane antigen, while glial fibrillary acidic protein and carcinoembryonic antigen were negative. Ultrastructural features included the presence of mitochondrial endoplasmic reticulum complexes, occasional desmosome-like junctions, and abundant extracellular matrix adherent to the tumor cells. We believe the cytomorphologic findings are characteristic and, when taken in concert with immunocytochemical and ultrastructural studies, allow differentiation of chordoma from other primary or metastatic neoplasms occurring in bone. As demonstrated in our series, chordoma is often an unsuspected diagnosis. We believe that FNA biopsy of these lesions can lead to a correct preoperative diagnosis and may also be utilized to document recurrence and thus facilitate the evaluation and management of patients with these lesions.

A stepwise procedure for evaluating irritant materials in normal volunteer subjects.

1. The cutaneous response to a known irritant has been assessed in human volunteer subjects using both clinical scoring and two non-invasive instrumental methods; erythema measurement using an erythema meter and capillary blood flow using a laser Doppler device. 2. Aqueous solutions (0.5% and 1%) of sodium hydroxide were applied to back skin for 3, 15 and 60 min with assessments immediately after removal and at 1, 24 and 48 hours. 3. Increased erythema was seen with increasing duration of exposure and an increase was also seen at 1 h, 24 h and 48 h after removal of the patch. The results obtained with the erythema meter paralleled the clinical erythema scores. However, the laser Doppler device showed the greatest changes immediately after removal of the patch with subsequent readings showing a gradual decrease. 4. Statistical analysis of the data has been carried out to determine the accuracy and precision of the assessment procedures and to determine the minimum test panel size for detecting irritant reactions. 5. Comparison between back and forearm skin indicated a greater sensitivity to sodium hydroxide on the back. 6. The results of this study define an ethical approach to testing irritant materials in human subjects and provide the basis for the development of a classification system for cutaneous irritants.

The effect of season on reproduction in dairy cattle.

A survey was carried out in North West Tasmania to compare the breeding performance of 2,068 cows in 27 dairy herds--15 herds calving in spring and 12 in autumn. The percentage of cows submitted to artificial insemination for the first time in the first 24 days of the mating period was 87% for the spring calving group and 75% for the autumn calving group. Figures for non-return-to-service rate over the subsequent 21 days were 72% and 55%, respectively. The difference in breeding performance associated with time of calving was not attributable to age, calving to mating interval or on cow condition or daily milk fat yield at 3 weeks (+/- 1 week) after the start of mating.

Under-utilization of the OTA Fracture Classification in the orthopaedic trauma literature.

BACKGROUND: The OTA Fracture Classification is designed to provide a common language and facilitate effective communication among orthopaedic surgeons. We attempted to measure the degree to which this classification is currently being utilized in orthopaedic trauma literature. METHODS: We reviewed all of the articles in the JOT in 2011. We determined which of these articles could have appropriately utilized the 2007 OTA Classification. We calculated the percentage that mentioned and correctly cited this classification system as a reference. RESULTS: There were 145 articles in 2011. One hundred of these articles were appropriate for classifying a fracture. 38% of these articles utilized the OTA classification in the text. Only 42% of articles mentioning the OTA Classification cited a reference. 38% of these citations used the old (1996) OTA Classification reference, and only 8% overall correctly cited the 2007 OTA Classification reference. 51% of articles mentioned some other classification system; 21 in addition to OTA and 30 instead of the OTA classification. CONCLUSIONS: The OTA Fracture Classification is being used more commonly (38%) but is not routinely used or correctly cited (8%) in articles currently being published in the Journal of Orthopaedic Trauma, despite the fact that it is "required" according to the instructions to authors. We conclude that future authors should utilize and correctly reference the 2007 OTA Classification so that the benefits of a common language can be realized. Routine and consistent utilization of the classification may ultimately lead to more consistency and improved interpretability of treatment outcomes in published orthopaedic trauma research. LEVEL OF EVIDENCE: Level-III case-control study, decision analysis.